TP53 mutations and MDM2SNP309 identify subgroups of AML patients with impaired outcome

• DOI: 10.1111/ejh.12438
• Publication Date: 2014-08-23T14:16:54Z
• Authors: Ingrid Jakobsen Falk; Kerstin Willander; Roza Chaireti; Johan Lund; Hareth Nahi; Monica Hermanson; Henrik Gréen; Kourosh Lotfi; Peter Söderkvist
• Keywords: SNP

Abstract Background TP 53 is commonly mutated in several cancers and confers treatment resistance poor prognosis. Altered expression of mouse double minute 2 ( MDM 2), a negative regulator p53, may also attenuate normal p53 signaling, thereby enhancing tumor transformation to apoptosis. The single nucleotide polymorphism SNP ) 309 has been reported increase impair response. Experimental design We investigated the frequency impact mutations mut) SNP309 on outcome overall survival OS 189 S wedish acute myeloid leukemia patients. genetic analyses were performed using SSCA direct sequencing (for exon 5–8 P yrosequencing ). Results found high (22%) mut patients with cytogenetic aberrations, association high‐risk cytogenetics < 0.001). had lower response rates (22% compared 76% CR wild‐type (wt) patients, 0.001) reduced (2 16 months, respectively, In wt or intermediate risk conferred an impaired outcome, carrying alternative G ‐allele having shorter T / (median 9 vs. 50 = 0.020). Conclusions Our results show that analysis genotyping be useful tools for prognostication, stratification, selection most likely benefit from new drugs targeting signaling pathway.